Description

Simple

A medication used to treat moderate to severe pain.

Clinical

A centrally-acting opioid agonist and SNRI (serotonin/norepinephrine reuptake inhibitor) used for the management of moderate to severe pain in adults.

Overview

Tramadol is a centrally acting synthetic opioid analgesic and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to [codeine] and [morphine]. Due to its good tolerability profile and multimodal mechanism of action, tramadol is generally considered a lower-risk opioid option for the treatment of moderate to severe pain. It is considered a Step 2 option on the World Health Organization's pain ladder and has about 1/10th of the potency of [morphine].

Tramadol differs from other traditional opioid medications in that it doesn't just act as a μ-opioid agonist, but also affects monoamines by modulating the effects of neurotransmitters involved in the modulation of pain such as serotonin and norepinpehrine which activate descending pain inhibitory pathways.[13] Tramadol's effects on serotonin and norepinephrine mimic the effects of other SNRI antidepressants such as [duloxetine] and [venlafaxine].

Tramadol exists as a racemic mixture consisting of two pharmacologically active enantiomers that both contribute to its analgesic property through different mechanisms and are also themselves metabolized into active metabolites: (+)-tramadol and its primary metabolite (+)-O-desmethyl-tramadol (M1) are agoni... Read more

Pharmacology

Indication

Tramadol is approved for the management of moderate to severe pain in adults.[29, Read more

Pharmacodynamic

Tramadol modulates the descending pain pathways within the central nervous system through the binding of parent and M1 metabolite to μ-opioid receptors and the weak inhibition of the reuptake of norepinephrine and serotonin.[ Read more

Mechanism of action

Tramadol is a centrally acting μ-opioid receptor agonist and SNRI (serotonin/norepinephrine reuptake-inhibitor) that is structurally related to [codeine] and [morphine]. Tramadol binds weakly to κ- and δ-opioid receptors and to the μ-opioid receptor with 6000-fold less affinity than morphine.[ Read more

Absorption

**Oral Administration**

Tramadol is administered as a racemate, with both the [-] and [+] forms of both tramadol and the M1 metabolite detected in circulation. Following administration, racemic tramadol is rapidly and almost completely absorbed, with a bioavailability of 75%. This difference in a... Read more

Protein binding

About 20% of the administered dose is found to bind to plasma proteins. Protein binding appears to be independent of concentrations up to 10μg/mL. Saturation only occurs at concentrations outside of the clinical range.[ Read more

Volume of distribution

The volume of distribution of tramadol is reported to be in the range of 2.6-2.9 L/kg.[29, Read more

Clearance

In clinical trials, the clearance rate of tramadol ranged from 3.73 ml/min/kg in renal impairment patients to 8.50 ml/min/kg in healthy adults.[29, Read more

Half life

Tramadol reported a half-life of 5-6 hours while the M1 metabolite presents a half-life of 8 hours.[ Read more

Route of elimination

Tramadol is eliminated primarily through metabolism by the liver and the metabolites are excreted primarily by the kidneys, accounting for 90% of the excretion while the remaining 10% is excreted through feces.[ Read more

Toxicity

The reported LD50 for tramadol, when administered orally in mice, is 350 mg/kg.[ Read more

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Dizziness US
  • Kind: experimental
    • Percent: 26
  • Clinical Trial
    Constipation US
  • Kind: experimental
    • Percent: 24
  • Clinical Trial
    Nausea US
  • Kind: experimental
    • Percent: 24
  • Clinical Trial
    Headache US
  • Kind: experimental
    • Percent: 18
  • Clinical Trial
    Somnolence US
  • Kind: experimental
    • Percent: 16
  • Clinical Trial
    Vomiting US
  • Kind: experimental
    • Percent: 9
  • Clinical Trial
    Pruritus US
  • Kind: experimental
    • Percent: 8
  • Clinical Trial
    CNS stimulation US
  • Kind: experimental
    • Percent: 7
  • Clinical Trial
    Asthenia US
  • Kind: experimental
    • Percent: 6
  • Clinical Trial
    Sweating US
  • Kind: experimental
    • Percent: 6
  • Clinical Trial
    Vasodilation US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Urinary Frequency US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Menopausal Symptoms US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Hypertonia US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Abdominal Pain US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Visual Disturbance US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Coordination disturbance US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Rash US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Anxiety US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Anorexia US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Sleep Disorder US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Euphoria US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Confusion US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Nervousness US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Flatulence US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Urinary Retention US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Miosis US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Malaise US
  • Kind: experimental
    • Percent: 1 - 5%
  • Clinical Trial
    Diarrhea US
  • Kind: experimental
    • Percent: 5
  • Clinical Trial
    Dry Mouth US
  • Kind: experimental
    • Percent: 5
  • Clinical Trial
    Dyspepsia US
  • Kind: experimental
    • Percent: 5
  • Clinical Trial
    Agitation US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Hyperreflexia US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Death US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Fever US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Dyspnea US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Anaphylaxis US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Tremor US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Tremor US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Shivering US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Amnesia US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Coma US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Menstrual disorder US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Seizures US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Depression US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Accidental injury US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Suicidal tendency US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Syncope US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Abnormal Gait US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing
    Urticaria US
  • Kind: experimental
    • Percent: <1%
  • Clinical Trial Post Marketing

    Contraindications

    • Regions: Canada
    • Excluded Age Groups:
      • pediatric
    • Below Age:
      • Amount: 12
      • Unit: year
    • Regions: Canada
    • Patient Conditions:
        • Name: Central nervous system depression
        • Drugbank Id: DBCOND0096632
    • Regions: Canada
    • Patient Conditions:
        • Name: Acute Head Injury
        • Drugbank Id: DBCOND0112466
    • Regions: Canada
    • With Categories Coadmin:
        • Name: Monoamine Oxidase Inhibitors
        • Drugbank Id: DBCAT001004
        • Mesh Id: D008996
    • Regions: Canada
    • Patient Conditions:
        • Name: Convulsive disorders
        • Drugbank Id: DBCOND0107830
    • Regions: Canada
    • Patient Conditions:
        • Name: Delirium Tremens (DTs)
        • Drugbank Id: DBCOND0107126
    • Regions: Canada
    • Patient Conditions:
        • Name: Acute alcoholism
        • Drugbank Id: DBCOND0107892
        • Modification Of:
          • Base:
            • Name: Alcoholism
            • Drugbank Id: DBCOND0006017
          • Severity:
            • Includes:
              • acute
    • Regions: Canada
    • Patient Conditions:
        • Name: Cor Pulmonale
        • Drugbank Id: DBCOND0042897
    • Regions: Canada
    • Patient Conditions:
        • Name: Respiratory Depression
        • Drugbank Id: DBCOND0034868
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe COPD
        • Drugbank Id: DBCOND0050607
        • Modification Of:
          • Base:
            • Name: COPD
            • Drugbank Id: DBCOND0043004
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Status Asthmaticus
        • Drugbank Id: DBCOND0001831
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe bronchial asthma
        • Drugbank Id: DBCOND0107864
        • Modification Of:
          • Base:
            • Name: Bronchial Asthma
            • Drugbank Id: DBCOND0031527
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe Hepatic Impairment
        • Drugbank Id: DBCOND0070791
        • Modification Of:
          • Base:
            • Name: Heptic Impairment
            • Drugbank Id: DBCOND0072269
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Severe Renal Impairment
        • Drugbank Id: DBCOND0045819
        • Modification Of:
          • Base:
            • Name: Renal Impairment
            • Drugbank Id: DBCOND0031781
          • Severity:
            • Includes:
              • severe
    • Regions: Canada
    • Patient Conditions:
        • Name: Suspected surgical abdomen
        • Drugbank Id: DBCOND0107886
    • Regions: Canada
    • Patient Conditions:
        • Name: Ileus
        • Drugbank Id: DBCOND0010794
    • Regions: Canada
    • Patient Conditions:
        • Name: Bowel Obstruction
        • Drugbank Id: DBCOND0031840
    • Regions: US
    • Patient Conditions:
        • Name: Intoxication
        • Drugbank Id: DBCOND0022957
    • Hypersensitivity:
      • true
    • Regions: US

    Food Interactions

    Avoid alcohol. Co-administration of alcohol may potentiate the CNS effects of tramadol.

    Take with or without food. Co-administration of food does not affect pharmacokinetics.